In an effort to boost the efficiency of drug development, a group of industry, academic, and government experts is seeking ways to streamline the US clinical trials process to improve quality while reducing costs and time requirements. But the group is not expected to issue recommendations for several years, meaning that the ongoing migration of US clinical trials overseas—especially India, Russia, China, and a host of Third World countries—is likely to continue for some time.
“We are seeing discovery and innovation at a quickening pace, yet the US is perceived by many as a sluggish and inefficient environment for clinical research,” said Judith Kramer, MD, associate professor of medicine at Duke University. “As a result, an increasing number of clinical trials of products destined for the US are actually conducted off-shore. We need to be able to conduct these trials here at home, because Americans are the target population for many of these products,” she said.
The number of clinical trials conducted in the US has dropped by 30 percent since 2001, said Dr. Kramer, who is also executive director of the Clinical Trials Transformation Initiative (CTTI), a public-private initiative established by the US Food and Drug Administration (FDA) and Duke last year to improve the quality and efficiency of US clinical trials. During the same period, the number of clinical trials in India registered with FDA jumped by more than 970% from 46 to 493, while those in China grew by more than 500% from 16 to 97, according to an analysis of FDA data by CenterWatch, an information-services company in Boston.
While these numbers may be a drop in the bucket compared to the nearly 15,000 open studies registered with the FDA in the US, the metrics and trends cannot be ignored. An increasing number of big pharmas, including GlaxoSmithKline and Wyeth Pharmaceuticals, have shifted the lion’s share of their clinical trial work to countries outside the US and Western Europe. The reasons are obvious: Conducting a clinical trial in India can be 50% to 60% cheaper than in the US, where testing a new drug averages $400 million.
Clinical trial work in India can be done more quickly than in the US, especially since the average trial time in the US increased by 70% to 780 days from 1999 and 2006, according to the Tufts University Center for the Study of Drug Development. The adage that time is money is especially true in pharmaceuticals, where each day saved in a clinical trial correlates to an additional day of marketing exclusivity, which translates into significant additional revenues, especially for blockbusters.
In addition to improving efficiency, making clinical trials safer is another prime goal for the FDA, which was roundly criticized last year by the inspector general (IG) of its parent Department of Health and Human Services. The IG found that FDA didn’t know how many clinical trials were underway or where they were being held and audited fewer than 1% of trial sites, not to check on participant safety but to verify the quality of the data two to three years after the trials had ended.
“A robust clinical trials system is essential to better protect the public and strengthen human subject protections,” said Rachel Behrman, MD, director of FDA’s Office of Critical Path Programs and co-chair of the CTTI executive board. “By modernizing the current clinical trial system, we will be able to more efficiently and effectively collect the needed data to answer the pressing questions about the use of medical products,” she said.
CTTI is assembling participants from government, industry (pharmaceuticals, biotech, medical devices), contract research organizations (CROs), and patient advocacy groups. Their recommendations are expected to encompass a broad range, including: establishing accreditation programs and national standards of research for clinical investigators and research sites; developing electronic forms to collect data and enter into contracts with hospitals and physician practices; exploring alternative models for institutional review boards (IRBs) to minimize duplication in multi-site clinical trials; and identifying ways to enhance participant informed consent.
“There is concern that our research system is falling behind the needs of society to determine the balance of benefit and risk from drugs, devices, and surgical procedures,” said Robert Califf, MD, vice chancellor for clinical research at Duke and CTTI co-chair. “We aim to provide a forum in which the experts in the field can put forward ideas about how to improve the system and then we can do research to inform policy makers about whether suggested changes are likely to have beneficial effects.”
Worldwide, the clinical trials enterprise generated about $50 billion in 2008 and is expected to grow 10% annually, according to Visiongain Ltd., a London-based consultancy. Much of the growth over the next 10 years is expected to come from outsourcing of clinical trials overseas, especially to China and India, as well as to domestic CROs.
While the conduct of clinical trials is becoming globalized, standards are far from universal. The FDA has adopted rules different than those proposed by the World Medical Association (WMA), whose Declaration of Helsinki guidelines are used by regulatory agencies in many countries to oversee clinical trials, including those for the US market.
In October, the WMA recommended placing limits on use of placebos and requiring that trials be registered in public databases prior to enrollment of subjects. The FDA implemented new rules permitting new drug applicants to bypass the Helsinki guidelines when conducting certain clinical trials overseas. The issue remains unresolved.
About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.
This article was published in Drug Discovery & Development magazine: Vol. 11, No. 12, December, 2008, pp. 8-9